Critical congenital heart disease (CCHD) is a major cause of neonatal morbidity and mortality. Pulse oximetry screening enables early detection, potentially reducing complications and improving outcomes. This study evaluated pediatric residents’ knowledge, attitudes, and practices (KAP) related to CCHD screening in Saudi Arabia. A cross-sectional survey was distributed to pediatric residents across Saudi Arabia. The questionnaire assessed knowledge, attitude, and practice regarding CCHD screening. A total of 123 pediatric residents in training were included in the study. Of these, 57 (46.3%) were male, and 66 (53.7%) were female. A progressive increase in mean scores was observed with advancing training years (p = 0.010). A significant difference was observed in knowledge scores based on completion of a cardiology rotation (p = 0.006). A progressive increase in attitude scores was observed with each successive year of training. Current year in training showed a statistically significant association with attitude scores (p < 0.001). Completion of a newborn nursery or NICU rotation was also significantly associated with higher attitude scores (p = 0.027). Similarly, attitude scores were significantly higher among those who had completed a cardiology rotation (mean = 12.99, SD = 1.52) compared to those who had not (mean = 11.60, SD = 1.84; p < 0.001). While practice scores were not statistically different across most groups, senior residents demonstrated better adherence to screening. Residents exhibit increasing awareness and positive attitudes with experience; however, practical implementation remains inconsistent. Targeted education and standardized protocols are necessary to improve outcomes. A positive correlation was observed between knowledge and attitude scores (r = 0.346, p < 0.001).
Functional analysis of SLC22A5 variants can improve diagnostic accuracy in patients with primary carnitine deficiency (PCD). Herein, we performed a genetic analysis of three neonates with PCD. Two of the patients harbored a novel synonymous SLC22A5 variant that has not been previously reported, and the other patient harbored a classical splice site variant. The splicing patterns of the two SLC22A5 variants were evaluated using three in silico tools, and in vitro minigene analysis was performed to verify the impact of variants on RNA splicing mechanisms. All three in silico tools predicted that both SLC22A5 variants could alter normal RNA splicing. Functional studies using minigene assays demonstrated that the c.450C>T (p.F150=) leads to partial exon 2 skipping, and c.394-1G>A leads to intron 1 retention and exon 2 skipping. Intron 1 retention of 65 nucleotides and exon 2 skipping were confirmed by sequencing cDNA amplification products. These results, along with functional evidence, led to reclassification of c.450C>T (p.F150=) and c.394-1G>A as likely pathogenic and pathogenic, respectively. This is the first reported synonymous variant in the SLC22A5 gene that has been functionally validated to affect RNA splicing, thus enriching the variant spectrum of SLC22A5 and aiding accurate PCD diagnosis.
CFTR modulators have transformed the clinical evolution of patients with CF. The number of pregnancies is increasing in women with CF, most of whom are now treated with CFTR modulators such as elexacaftor/tezacaftor/ivacaftor (ETI) or Tezacaftor/Ivacaftor. This raises some questions as we still lack data on foetal and maternal safety. The preliminary data seem to support the continuation of modulators. Some of these mothers may also give birth to newborns with CF and this raises more questions. We report here four cases of CF newborns whose mothers were treated with CFTR modulators throughout pregnancy to help refine potential foetal outcomes of in utero administration of CF modulators. No maternal or foetal complications could be attributed to CFTR modulators. Three CF newborns were exposed to ETI and were false negative of the newborn screening. Two of them were pancreatic sufficient at birth. The remaining patient, exposed to Tezacaftor/Ivacaftor (TI) alone, showed elevated immunoreactive trypsin (IRT) and severe pancreatic insufficiency at birth. These cases highlight that in utero administration of ETI could potentially improve neonatal outcomes of CF newborns and cause newborn screening false negative.
Screening for spinal muscular atrophy (SMA) was adopted by all US state newborn screening programs between 2018 and 2024; by the end of 2022, 48 states were screening for SMA. We assessed trends in health insurance records of SMA diagnoses to quantify improvements in the timeliness of SMA identification following the adoption of screening. We used nationally representative Medicaid claims data for approximately half of US births covered by public insurance and a convenience sample of employer-sponsored health plans. We analyzed records for birth cohorts with at least 1 full year of follow-up (i.e., through the end of the following calendar year). For 2017 births, 1.3 per 100,000 infants had SMA codes first recorded by 1 month of age; this increased to 6.6 per 100,000 among publicly insured newborns born in 2022. The rollout of SMA newborn screening across US states was also followed by improvements in the timely detection of SMA. The proportion of infants with SMA detected by 1 month increased from 18% in 2017 to 61% in 2021 and is projected to reach 75% in 2022. Growth in timely detection was even greater in the employer-insured sample. Timely diagnosis of SMA can enable the initiation of treatment prior to the irreversible loss of motor function.
In 2023, the Russian Federation expanded its national newborn screening (NBS) program from 5 to 36 conditions, 29 of which are inherited metabolic diseases (IMDs). This study presents the first nationwide results and outcomes of the expanded NBS program. Between January 2023 and December 2024, dried blood spots from 2,466,615 newborns (98.53% of the birth cohort) were analyzed for IMDs using MS/MS. Screen-positive cases were referred to the national reference center for confirmatory testing, which included biochemical (MS/MS and GC-MS) and genetic analyses (NGS). A total of 41,728 neonates (1.69%) screened positive, of whom 37,733 underwent confirmatory testing. It resulted in 834 confirmed diagnoses of IMDs (1 in 2900 live births). Phenylketonuria was the most prevalent IMD (n = 538; 1 in 4600), followed by MCADD (n = 99; 1 in 25,000). Distinct regional and ethnic variations were observed, including a high prevalence of tyrosinemia type 1 in the Chechen Republic and MCADD in North Ossetia. The integration of NGS was essential for resolving complex cases, such as identifying heterozygous carriers and dual diagnoses. These findings underscore the program’s clinical utility, highlight unique epidemiological patterns, and identify challenges such as false positives and diagnostic complexities, which will guide future refinements.
